Fluid status is an important issue in long-term dialysis patients and is related to clinical outcome. In fact, knowledge of a patient's fluid status is essential in efficiently managing hemo- as well as peritoneal-dialysis patients. Chronic fluid overload is associated with left ventricular hypertrophy, left ventricular dilatation, arterial hypertension, and eventually the development of congestive heart failure. High interdialytic weight gain on top of chronic fluid overload further increases the burden for the cardiovascular system. Recent studies have shown that fluid overload can even be linked to an increased mortality (Wizemann V. et al., “The mortality risk of overhydration in haemodialysis patients”, Nephrol. Dial. Transplant 2009, 24:1574-1579). Management of the fluid status involves restriction of sodium intake and, to the extent possible and over time, attainment of a post-dialysis weight equal to the patient's dry weight.
The determination, achievement, and maintenance of dry weight are challenging because of the absence of appropriate technologies for estimating dry weight. Consequently, the physician's prescription for the clinical post-dialytic target weight is usually based on clinical indicators and unfortunately is often no more than an informed guess. Fluid overload can be expressed as excess extracellular fluid volume (ECV). In order to have a comparative standard for a reference to body mass, body composition or total body water (TBW) is required.
Dry weight may be defined as the weight at which an individual is as close as possible to a physiological fluid status without experiencing symptoms indicative of fluid overload or deficit. Clinically, dry weight is determined as the lowest weight a patient can tolerate without developing intra- or interdialytic symptoms of hypovolemia. This definition is flawed since it does not take into account patients with myocardial or autonomic system disease in whom symptoms may occur with gross fluid overload, i.e., these patients may exhibit symptoms which would indicate they are at dry weight when, in fact, they are fluid overloaded. Clinical assessment is also hampered by the fact that some liters of fluid may accumulate in the body before edema becomes clinically evident and that it does not account for changes in lean body mass, fat mass or nutritional status over time. Consequently, a majority of dialysis patients may be fluid overloaded with or without specific symptoms.
Various approaches towards a more objective measure of dry weight have been developed, such as blood volume monitoring, ultrasound assessment of inferior vena cava diameter, and several biochemical parameters, such as brain or atrial natriuretic peptide. None of these measures, however, gives a recognized accurate estimate of dry weight due to the fact that they have not been proved to be practical or reliable in the detection of dry weight in individual patients.
Isotope dilution methods are frequently recommended for fluid volume measurement (ECV or TBW), but they are clinically not feasible because of technical complexity and expense. These methods can determine the absolute quantities of ECV and TBW but cannot determine the amount of excess extracellular water (fluid overload) because they do not provide a dry weight value.
Efforts have been made in the past to use bioimpedance technology to facilitate the dry weight prescription process. See, for example, Kuhlmann et al., “Bioimpedance, dry weight and blood pressure control: new methods and consequences”, Current Opinion in Nephrology and Hypertension, 2005, 14:543-549, the disclosure of which is entirely incorporated by reference.
Several different bioimpedance approaches to determine dry weight have been published:
The normovolemic-hypervolemic slope method (see, e.g. Chamney et al., “A new technique for establishing dry weight in hemodialysis patients via whole body bioimpedance”, Kidney Int., 2002, 61:2250-2258, the disclosure of which is entirely incorporated by reference) applies whole body multi-frequency bioimpedance to assess pre-dialytic total body extracellular fluid volume and compares the extracellular fluid volume/body weight relation at hypervolemia with the standard value in normovolemic individuals.
The resistance-reactance graph method (see, e.g. Piccoli et al., “A new method for monitoring body fluid variation by bioimpedance analysis: the RXc graph”, Kidney Int., 1994, 46:534-539, the disclosure of which is entirely incorporated by reference) uses whole body single frequency bioimpedance at 50 kHz for assessment of fluid status and nutritional status from height-adjusted resistance and reactance. The resulting resistance-reactance vector is set in relation to a distribution range in a normovolemic population. The difficulty of this method is that it does not provide absolute values of the fluid status—patients can only be compared to percentiles of a normal population.
“Whole body” bioimpedance spectroscopy (wBIS) is a noninvasive technique calculating the whole body extracellular fluid volume (wECV) and the whole body intracellular fluid volume (wICV) by measuring resistance and reactance over a range of alternating current frequencies (e.g. 50 to 250 frequencies from ca. 1 kHz to 1000 kHz). Ratios of wECV or wICV to total body water volume (TBW) or the ratio wECV/wICV are used to assess the fluid status of a patient (Wei Chen et al., “Extracellular Water/Intracellular Water Is a Strong Predictor of Patient Survival in Incident Peritoneal Dialysis Patients”, Blood Purif., 2007, 25:260-266, the disclosure of which is entirely incorporated by reference).
The newest and more sophisticated technique is a whole body bioimpedance spectroscopy with a physiological tissue model: wECV and wTBW are measured by whole body bioimpedance spectroscopy and additionally the fluid status and body composition are calculated. This is achieved by setting the measured patient in relation to a subject with a normal fluid status and the same body composition. Thus it relates back to the normohydrated properties of tissue. This physiologic tissue model is described in “A whole-body model to distinguish excess fluid from the hydration of major body tissues”, Chamney P. W., Wabel P., Moissl U. M. et al., Am. J. Clin. Nutr., 2007, January, 85(1):80-9, the disclosure of which is entirely incorporated by reference. This method allows the patient specific prediction of the normal fluid status and the normal fluid status weight—the weight, the patient would have with a working kidney. However the accuracy of this method can be influenced by degrees of fluid overload.
An additional method is based on measurement of calf normalized resistivity (CNR) at different fluid status of pre-dialysis or post-dialysis with comparison of the results to a normal population (Zhu F, Kotanko P, Levin W. N. et al., Estimation of Normal Hydration in Dialysis Patients using Whole Body and Calf Bioimpedance Analysis. Physiol. Meas., 2011, 32:887-902, the disclosure of which is entirely incorporated by reference).
A conceptually different method (see, for example, Zhu et al., “Adjustment of dry weight in hemodialysis patients using intradialytic continuous multifrequency bioimpedance of the calf”, Int. J. Artif Organs, 2004, 12:104-109 and Zhu et al., “A method for the estimation of hydration state during hemodialysis using a calf bioimpedance technique”, Physiol. Meas., 2008: S503-S516, the disclosures of which are entirely incorporated by reference) uses segmental bioimpedance in the form of intradialytic calf bioimpedance to record changes in calf resistance or resistivity which is equivalent to extracellular fluid volume during dialysis (in the following: cBIS). Dry weight determined by this method (DWcBIS) is defined as the body weight at which calf extracellular volume is not further reduced despite ongoing ultrafiltration. Although this method is good for estimating DWcBIS of a patient, the technique requires the performance of bioimpedance measurements throughout a dialysis session. Dry weight cannot be predicted by this method. In addition, patient movement at the lower limb is limited during the dialysis session and measuring electrodes have to be kept in place until the session is finished.
Despite the fact that the aforementioned methods are widely used in clinics throughout the world, there exists a need for improved methods for monitoring the fluid status of a fluid-overloaded patient which are easy to implement and/or generate reliable dry weight estimations, in particular when a severely overloaded patient needs to be brought to his/her normal fluid status or dry weight. In other words, it would be beneficial for the adequate fluid management of dialysis patients to quantify fluid overload and to be able to estimate the dry weight more reliably during the reduction of fluid overload than currently done in clinical practice. Furthermore, an urgent need exists for treatment of a patient based on such monitoring in particular to avoid intradialytic symptoms.